Background antibody secreting cells, recognized as plaque forming cells (bkg PFC) in spleens of non-immunized mice, are unique immunocytes. These cells have been shown to be distinct from other antibody secreting cells in a number of ways. They do not participate in the primary response, do not increase or decrease appreciably in number with age after birth and are uninhibited by antibody directed against the specific antigen in question in addition to other important differences. While the function of bkg PFC is unknown, indications are that they are associated with natural immunity. The antibody secreted by these cells may serve a dual function, as a recognition element and as a regulator of the immune response to the low level of ubiquitous antigens in the normal environment. Background antibody secretors will be screened for their response to a number of different natural antigens. These will include ribonuclease, ovalbumin, thyroglobulin, tobacco mosaic virus and sheep RBC. Studies will concentrate on the relationship of bkg PFC to the number of distinct antigenic determinants on each molecule or RBC, and to possible changes in this relationship with age. Groups of mice will be subjected to chemical stress of Vinblastine or regular bleeding. The replenishment of bone marrow and subsequent effect on appearance or disappearance of background PFC will be monitored with respect to all antigens described. Spleen cell fractionation experiments and other procedures will be employed for characterizing the bkg PFC. The cells will be cultured on Millipore filters floating on the surface nutrient agarose dishes, so that frequent transfers of the cells to appropriate antigen agar dishes can be accomplished while the products of cell secretions can be revealed in the underlying agarose.